Alcohol consumption is a major etiology of chronic liver disease worldwide. The morphological spectrum of human alcoholic liver disease includes fatty liver, alcoholic hepatitis, and cirrhosis. In rodents, intragastric infusion of ethanol for 4-5 weeks leads to steatosis, inflammation, and to a less extent fibrosis in the liver, whereas feeding Lieber-DeCarli liquid diet containing ethanol does not cause significant liver injury except steatosis. In humans, interestingly, only a small percentage of heavy drinkers (10-15%) developed alcoholic liver injury, strongly suggesting that alcohol is a cofactor for developing chronic liver disease. Accumulating evidence suggests that many genetic and acquired factors are implicated in the susceptibility of the individual to alcohol-induced liver injury. These factors include chronic viral infection, nutritional factors, the dose and duration of alcohol consumption, pattern drinking, age of onset of drinking, genetic polymorphisms of cytokines and alcohol-metabolizing enzymes, gender, histocompatibility antigens, immunological factors, genetic predisposition to alcohol addiction, and hepatic iron overload. It has been well documented that alcohol consumption accelerates the development and progression of liver disease induced hepatitis virus infection. Our lab is to study how chronc ethanol consumption potentiates liver injury induced by other toxins or virus via dis-regulation of cytokine signals. We have demonstrated (1) that alcohol consumption accelerates T cell-mediated hepatitis via dis-regulation of NF-kappa B and STAT signaling pathways, (2) treatment with IL-6 ameliorates alcoholic fatty liver disease in mice.